Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality in surgical patients. National estimates suggest 1,062,000 PPCs per year, with 46,200 deaths, and 4.8 million additional days of hospitalization. Abdominal surgery is the field with the largest absolute number of PPCs. Our long-term goal is to develop and implement perioperative strategies to eliminate PPCs. Whereas PPCs are as significant and lethal as cardiac complications, research in the field has received much less attention, and strategies to minimize PPCs are regrettably limited. Recent clinical data support a crucial role for intraoperative ventilatory strategies in reducing PPCs, consistent with findings o the major effect of protective ventilation in reducing mortality in the Acute Respiratory Distress Syndrome (ARDS). Surprisingly, intraoperative ventilatory strategies are not at all included in current clinical recommendations to reduce PPCs. Surgical patients differ substantially from ARDS patients as most have no or limited lung injury at the onset of mechanical ventilation during general anesthesia. Yet, intraoperative anesthetic and surgical interventions can predispose to or produce direct and indirect lung injury. Superimposition of mechanical ventilation to these insults can facilitate the development of lung injury. Thus, ventilatory strategies aiming at lung protection in this large and underserved group of patients are greatly needed. Recent data suggest that positive end-expiratory pressure (PEEP) could be a major factor to reduce PPCs after abdominal surgery, a finding consistent with intraoperative physiological insults and experimental data. Accordingly, individualization of PEEP settings could be key to maximize outcomes. Yet, no study to date addressed methods to specifically optimize intraoperative PEEP, nor its effect on pulmonary outcomes. We hypothesize that optimal individualized intraoperative lung recruitment during abdominal surgery reduces the incidence of PPCs in patients at moderate and high-risk for them. We will leverage a collaboration among three academic US centers to study that hypothesis in the following aims: Aim 1. To characterize usual-care practices for mechanical ventilation during abdominal surgery in major US academic centers. Aim 2. To prospectively compare two methods to individualize PEEP settings in the operating room during abdominal surgery: (1) maximization of lung compliance during a decremental PEEP titration, and (2) prevention of negative end-expiratory transpulmonary pressures by measuring esophageal balloon pressures. With these Aims, we will determine the control (Aim 1) and intervention (Aim 2) ventilatory settings for the full-scale trial. Aim 3. To establish the processes required for the implementation of the full- scale multi-center clinical trial. At the conclusion of these aims, we will have the necessary and sufficient data to launch a multicenter clinical trial to establish the effect of optimal PEEP settings to prevent PPCs after abdominal surgery. Accordingly, our project could result in a major change in clinical practice and paradigm on intraoperative mechanical ventilation.